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Regen Eng Transl Med. 2018 Jun;4(2):92-103. doi: 10.1007/s40883-018-0052-4. Epub 2018 Apr 23.

Localized SDF-1α Delivery Increases Pro-Healing Bone Marrow-Derived Cells in the Supraspinatus Muscle Following Severe Rotator Cuff Injury.

Author information

1
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA.
2
School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA.
3
Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA.
4
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA.
5
Winship Cancer Institute, Emory University, Decatur, GA.
6
Wilmington Health Orthopedic Medical Center, Wilmington, NC.
7
Department of Orthopedics, Emory University, Decatur, GA.
8
Atlanta Veteran's Affairs Medical Center, Decatur, GA.

Abstract

To examine how the chemotactic agent stromal cell-derived factor-1alpha (SDF-1α) modulates the unique cellular milieu within rotator cuff muscle following tendon injury, we developed an injectable, heparin-based microparticle platform to locally present SDF-1α within the supraspinatus muscle following severe rotator cuff injury. SDF-1α loaded, degradable, N-desulfated heparin-based microparticles were fabricated, injected into a rat model of severe rotator cuff injury, and were retained for up to 7 days at the site. The resultant inflammatory cell and mesenchymal stem cell populations were analyzed compared to uninjured contralateral controls and, after 7 days, the fold-change in anti-inflammatory, M2-like macrophages (CD11b+CD68+CD163+, 4.3X fold-change) and mesenchymal stem cells (CD29+CD44+CD90+, 3.0X, respectively) was significantly greater in muscles treated with SDF-1α loaded microparticles than unloaded microparticles or injury alone. Our results indicate that SDF-1α loaded microparticles may be a novel approach to shift the cellular composition within the supraspinatus muscle and create a more pro-regenerative milieu, which may provide a platform to improve muscle repair following rotator cuff injury in the future.

KEYWORDS:

heparin; macrophages; mesenchymal stem cells; microparticles; stromal cell-derived factor-1α

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